Wen Ai-Qing, Gu Wei, Wang Jun, Feng Kai, Qin Liu, Ying Chen, Zhu Pei-Fang, Wang Zheng-Guo, Jiang Jian-Xin
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, P. R. China.
Shock. 2010 Jun;33(6):576-82. doi: 10.1097/SHK.0b013e3181cc0a8e.
Recent reports have indicated that IL-1[beta] is excessively released into the circulation during sepsis, and the expression level is closely correlated with the clinical course. Polymorphisms in the promoter region of IL-1B have been shown to affect LPS-induced IL-1[beta] transcription in vitro and IL-1[beta] plasma levels in healthy adults and to confer susceptibility to inflammatory diseases. However, it is not clear whether they confer susceptibility to sepsis after major trauma. The aim of this study was to search for association of polymorphisms (-1470G/C, -511T/C, and -31C/T) in the IL-1B gene promoter with the susceptibility to sepsis in a cohort of 238 major trauma patients. Genotyping of each patient for the three single-nucleotide polymorphisms was performed by restriction fragment length polymorphism-polymerase chain reaction method. Multivariate logistic regression analysis showed that the -1470 and -31 polymorphisms were associated with IL-1[beta] production by peripheral leukocytes in response to ex vivo LPS stimulation in an allele dose-dependent manner. Moreover, trauma patients carrying the -1470G or -31T alleles were more likely to develop sepsis compared with those with the -1470C or -31C allele (P = 0.014 and P = 0.038, respectively). Of the eight possible haplotypes composed of the three loci, the GCT and CTC haplotypes were associated with significantly higher and lower IL-1[beta] secretion (P = 0.005 and P = 0.035, respectively). Moreover, the GCT haplotype imparted higher risk of sepsis after severe injury (P = 0.04; odds ratio, 1.131; 95% confidence interval, 1.013-1.678). GCT homozygote patients also showed higher multiple organ dysfunction scores than CTC homozygote patients (P = 0.048). These data suggest that the IL-1[beta] promoter polymorphisms -1470G/C, -511T/C, and -31C/T may be functional both in vitro and in vivo. It may be possible to use these polymorphisms as relevant risk estimates for sepsis in trauma patients.
近期报告表明，在脓毒症期间白细胞介素-1β（IL-1β）会过度释放到循环系统中，其表达水平与临床病程密切相关。白细胞介素-1β（IL-1B）启动子区域的多态性已被证明在体外会影响脂多糖（LPS）诱导的IL-1β转录，在健康成年人中会影响IL-1β血浆水平，并使人易患炎症性疾病。然而，尚不清楚这些多态性是否会使严重创伤后的患者易患脓毒症。本研究的目的是在一组238例严重创伤患者中，寻找IL-1B基因启动子多态性（-1470G/C、-511T/C和-31C/T）与脓毒症易感性之间的关联。通过限制性片段长度多态性-聚合酶链反应方法对每位患者的这三种单核苷酸多态性进行基因分型。多变量逻辑回归分析表明，-1470和-31多态性以等位基因剂量依赖的方式与外周血白细胞在体外LPS刺激下产生IL-1β有关。此外，与携带-1470C或-31C等位基因的创伤患者相比，携带-1470G或-31T等位基因的患者更易发生脓毒症（P分别为0.014和0.038）。在由这三个位点组成的八种可能单倍型中，GCT和CTC单倍型分别与显著更高和更低的IL-1β分泌相关（P分别为0.005和0.035）。此外，GCT单倍型使严重损伤后发生脓毒症的风险更高（P = 0.04；比值比，1.131；95%置信区间，1.013 - 1.678）。GCT纯合子患者的多器官功能障碍评分也高于CTC纯合子患者（P = 0.048）。这些数据表明，IL-1β启动子多态性-1470G/C、-511T/C和-31C/T在体外和体内可能都具有功能。有可能将这些多态性用作创伤患者脓毒症的相关风险评估指标。
